GRAND

GRAND
ROUNDS
ROUNDS
September 1, 2006 September 1, 2006
Denise A. John Denise A. John
St. Thomas Hospital St. Thomas Hospital
Case
Case
! ! HPI HPI: : 60 60 y/o y/o ! ! presents for an eye exam. presents for an eye exam.
! ! ocular ocular c/o c/o s s
! ! ROS ROS: : (+) L temporal headache (+) L temporal headache
! ! All other systems unremarkable All other systems unremarkable
! ! FHX FHX: : Diabetes; HTN, stroke Diabetes; HTN, stroke
! ! SHX SHX: : Quit ETOH Quit ETOH 04; tobacco/IVDA 04; tobacco/IVDA
! ! Allergies Allergies: : NKDA NKDA
Ocular Exam
Ocular Exam

NLP NLP
! ! V V
A SC A SC
CF CF 4ft 4ft " " 20/200 20/200
! ! Motility Motility: Full OU : Full OU

4 4
! ! IOP IOP

8 8
! ! Pupils Pupils: (+) RAPD OD : (+) RAPD OD
NO VIEW
B-Scan: Funnel-shaped
retinal detachment
Differential Diagnosis
Differential Diagnosis
! ! Infectious Infectious
! ! Indolent CMV retinitis Indolent CMV retinitis
! ! Toxoplasma Toxoplasma retinitis retinitis
! ! Acute retinal necrosis (ARN) Acute retinal necrosis (ARN)
! ! Progressive outer retinal Progressive outer retinal
necrosis (PORN) necrosis (PORN)
! ! Choroidal Choroidal pneumocystosis pneumocystosis
! ! Cryptococcal Cryptococcal choroiditis choroiditis
! ! Tuberculosis Tuberculosis
! ! Candidiasis Candidiasis
! ! Syphilis Syphilis
! ! Neoplastic Neoplastic
! ! Ocular lymphoma Ocular lymphoma
! ! Metastasis Metastasis
! ! Inflammatory Inflammatory
! ! Sarcoidosis Sarcoidosis
! ! Vasculitides Vasculitides
More Info
More Info

! ! PMHX PMHX: :
! ! HIV/AIDS ( HIV/AIDS (Dx Dx 04) 04)
! ! CD4: 155 cells/mm CD4: 155 cells/mm
3 3
(5/05) (5/05)
! ! HIV nephropathy HIV nephropathy
! ! Hepatitis C Hepatitis C
! ! Chronic anemia Chronic anemia
! ! HTN HTN
! ! Chickenpox Chickenpox
! ! POHX POHX: :
! ! S/p steel injury OD S/p steel injury OD
! ! HZO OS (5/05) HZO OS (5/05)
! ! Conjunctivitis Conjunctivitis
! ! Keratitis Keratitis
! ! Uveitis Uveitis
! ! Post-herpetic Neuralgia Post-herpetic Neuralgia
! ! MEDS MEDS: :
! ! Acyclovir 400mg QID; HAART; Acyclovir 400mg QID; HAART;
lisinopril lisinopril; ; atenolol atenolol; ; bactrim bactrim; ;
Refresh PM Refresh PM
! ! External Exam External Exam: :
! ! Left hypo-pigmented scar: CNV Left hypo-pigmented scar: CNV
1 1
distribution distribution
! ! LUL LUL Entropion Entropion & & trichiasis trichiasis
! ! SLE SLE: :
! ! OD: OD: Shallow AC; 360 Shallow AC; 360 posterior posterior
synechiae synechiae; ; white cataract white cataract
! ! OS: OS: PEE; posterior PEE; posterior synechiae synechiae; ;
AC AC rxn rxn; 2-3+ NSC/3-4+ PSC; ; 2-3+ NSC/3-4+ PSC;
vitritis vitritis
Epidemiology: HIV
Epidemiology: HIV
! ! 40 million individuals infected worldwide 40 million individuals infected worldwide
! !
~ ~
900,000 in the U.S. 900,000 in the U.S.
! ! 70-80% treated for a HIV-related eye disorder 70-80% treated for a HIV-related eye disorder
! ! CD4 count may be used to predict the occurrence of CD4 count may be used to predict the occurrence of
specific ocular infections specific ocular infections
CD4 Count & Ocular
CD4 Count & Ocular
Infections
Infections
! ! < 500 cells/mm < 500 cells/mm
3 3
! ! Kaposi sarcoma Kaposi sarcoma
! ! Tuberculosis Tuberculosis
! ! Lymphoma Lymphoma
! ! < 250 cells/mm < 250 cells/mm
3 3
! ! Pneumocystosis Pneumocystosis
! ! Toxoplasmosis Toxoplasmosis
! ! < 100 cells/mm < 100 cells/mm
3 3
! ! Conjunctival Conjunctival/retinal /retinal
microvasculopathy microvasculopathy
! ! CMV retinitis CMV retinitis
! ! Most common Most common
! ! VZV retinitis VZV retinitis
! ! 2 2
nd nd
most common most common
! ! Cryptococcosis Cryptococcosis
! ! Microsporidiosis Microsporidiosis
CMV Retinitis
CMV Retinitis
! ! Occurs in Occurs in
immunocompromised immunocompromised
! ! Slow progression Slow progression
! ! Starts in periphery Starts in periphery
! ! Spreads along retinal Spreads along retinal
vasculature towards vasculature towards
posterior pole posterior pole
! ! Dense white/granular Dense white/granular
opacification opacification (full-retinal (full-retinal
thickness) thickness)
! ! Hemorrhage Hemorrhage
! ! Mild Mild vitritis vitritis
Acute Retinal Necrosis
Acute Retinal Necrosis
! ! Occurs in Occurs in immunocompetent immunocompetent
! ! > > 1 foci of full-thickness 1 foci of full-thickness
retinal necrosis with retinal necrosis with
discrete borders discrete borders
! ! Spreads 360 Spreads 360
circumferentially in circumferentially in
peripheral retina peripheral retina
! ! Posterior pole involvement Posterior pole involvement
is spared until late is spared until late
! ! Vasculitis Vasculitis
! ! Prominent inflammatory Prominent inflammatory
reaction (AC & vitreous reaction (AC & vitreous) )
Progressive
Progressive
Outer Retinal
Outer Retinal
Necrosis
Necrosis
PORN
PORN
! ! Rare form of necrotizing herpetic retinopathy Rare form of necrotizing herpetic retinopathy
! ! First described by Forster et al. (1990) First described by Forster et al. (1990)
! ! 2 pts: 2 pts: Fulminant Fulminant outer retinal necrosis sparing the inner outer retinal necrosis sparing the inner
retina & vasculature retina & vasculature
! ! Occurs in the Occurs in the immunocompromised immunocompromised: :
! ! Immunosuppressed Immunosuppressed organ-transplant recipients organ-transplant recipients
! ! Immune-deficient individuals: Immune-deficient individuals:
! ! Cancer Cancer
! ! Advanced AIDS Advanced AIDS
Pathogenesis
Pathogenesis
! ! Varicella Varicella-Zoster Virus -Zoster Virus
! ! Virus remains latent in sensory ganglia Virus remains latent in sensory ganglia
! ! Reactivated during times of loss of T-cell regulatory control Reactivated during times of loss of T-cell regulatory control
! ! Difficult to isolate/grow in-vitro Difficult to isolate/grow in-vitro
! ! Only organism isolated in the retina via culture, PCR & Only organism isolated in the retina via culture, PCR &
direct fluorescent antibody assay direct fluorescent antibody assay
PORN
PORN
! ! Engstrom Engstrom, et al. PORN: A variant of necrotizing , et al. PORN: A variant of necrotizing
herpetic retinopathy in patients with AIDS. herpetic retinopathy in patients with AIDS. Ophth Ophth
1994. 1994. 38 38 ! ! pts (65 eyes): pts (65 eyes): CD4 count: 21 cells/mm CD4 count: 21 cells/mm
3 3
(0-130 cells/mm (0-130 cells/mm
3 3
) )
! ! Largest study on PORN Largest study on PORN
! ! Retrospective chart review Retrospective chart review
! ! Median Median f/u f/u 3 months (0-10 months) 3 months (0-10 months)
! ! Objective: Characterize the clinical features & course Objective: Characterize the clinical features & course
PORN
PORN
! ! History of History of cutaneous cutaneous zoster zoster : 67% (22/33 pts) : 67% (22/33 pts)
! ! 41%: involved CNV 41%: involved CNV
1 1
! ! 12 of 15 pts: PORN occurred after a median of 2 12 of 15 pts: PORN occurred after a median of 2
months (2 months months (2 months 2 years) 2 years)
! ! 3 of 15 pts: PORN occurred concurrently 3 of 15 pts: PORN occurred concurrently
! ! 12 of 38 pts: Taking oral acyclovir at the time 12 of 38 pts: Taking oral acyclovir at the time
PORN was diagnosed PORN was diagnosed
! ! 50%: Acyclovir 800mg 5x/day 50%: Acyclovir 800mg 5x/day
Clinical Features
Clinical Features
! ! Ocular complaints Ocular complaints
! ! # # vision: Most common (54% eyes) vision: Most common (54% eyes)
! ! Constriction of visual fields (28% eyes) Constriction of visual fields (28% eyes)
! ! Floaters (11% eyes) Floaters (11% eyes)
! ! Pain (6% eyes) Pain (6% eyes)
! ! 7 pts with unilateral symptoms had asymptomatic 7 pts with unilateral symptoms had asymptomatic
disease in the fellow eye disease in the fellow eye
Clinical Features
Clinical Features
! ! Usually bilateral disease Usually bilateral disease
! ! 28 of 38 pts: Unilateral disease at diagnosis 28 of 38 pts: Unilateral disease at diagnosis
! ! 2 2
nd nd
eye became affected in 17 pts eye became affected in 17 pts " " median of 10 days median of 10 days
after diagnosis (3 days after diagnosis (3 days 4 weeks) in 6 pts 4 weeks) in 6 pts
! ! Intraocular inflammation is minimal to absent Intraocular inflammation is minimal to absent
! ! 23 of 60 eyes: Anterior segment inflammation 23 of 60 eyes: Anterior segment inflammation
! ! 61% mild AC reaction 61% mild AC reaction
! ! 11% 11% keratic keratic precipitates (fine, white deposits) precipitates (fine, white deposits)
! ! 6% posterior 6% posterior synechiae synechiae
! ! 15 of 61 eyes: Vitreous inflammation 15 of 61 eyes: Vitreous inflammation
! ! 80% mild 80% mild vitritis vitritis
Clinical Features
Clinical Features
! ! Multifocal Multifocal, discrete lesions of the outer retina , discrete lesions of the outer retina " " rapidly rapidly
progress to confluence & full-thickness retinal involvement progress to confluence & full-thickness retinal involvement
! ! Perivenular Perivenular lucency lucency
Clinical Features
Clinical Features
! ! Characteristic macular Characteristic macular
lesion lesion: :
! ! Parafoveal Parafoveal opacification opacification
with a with a cherry-red spot cherry-red spot
! ! contiguous with contiguous with
peripheral lesions peripheral lesions
! ! Peripheral lesions Peripheral lesions + +
posterior pole posterior pole
! ! Zone 1: 32% eyes Zone 1: 32% eyes
! ! lesions only in zone 1 lesions only in zone 1
! ! Zone 2: 72% eyes Zone 2: 72% eyes
! ! Zone 3: 86% eyes Zone 3: 86% eyes
! ! 28% eyes all 3 zones 28% eyes all 3 zones
Clinical Features
Clinical Features
! ! Disease quiescence Disease quiescence
! ! Dense white plaques: Dense white plaques:
cracked mud cracked mud
appearance appearance
! ! Atrophic areas Atrophic areas + + holes holes
Clinical Features
Clinical Features
! ! Other manifestations Other manifestations: :
! ! 11 of 65 eyes: 11 of 65 eyes: Optic nerve abnormalities Optic nerve abnormalities
! ! Disc swelling Disc swelling
! ! Hyperemia Hyperemia
! ! Atrophy Atrophy
! ! 11 of 29 pts: 11 of 29 pts: Afferent Afferent pupillary pupillary defect defect
! ! 13 of 61 eyes: 13 of 61 eyes: Retinal Retinal vasculopathy vasculopathy
! ! Vascular sheathing/occlusion Vascular sheathing/occlusion
! ! Areas within or near retinal necrosis Areas within or near retinal necrosis
FA: PORN
FA: PORN
! ! Walton et al. FA in PORN. Walton et al. FA in PORN.
Retina 16: 1996 Retina 16: 1996
! ! Early Early: : Microvascular Microvascular changes changes
" " equatorial & peripheral retina equatorial & peripheral retina
! ! Confluent retinal disease Confluent retinal disease: : # #
retinal vasculature & loss of retinal vasculature & loss of
capillaries; RPE damage; capillaries; RPE damage;
choriocapillaris choriocapillaris leakage leakage
! ! Reactivation Reactivation: Brush-fire pattern : Brush-fire pattern
of of choroidal choroidal leakage at lesion leakage at lesion
border border
! ! PORN = PORN = Retinochoroiditis Retinochoroiditis
Management: PORN
Management: PORN
! ! Exact combination of Exact combination of antivirals antivirals & duration of & duration of
treatment not known treatment not known
! ! Guided by anecdotal information Guided by anecdotal information
! ! Herpes-zoster traditionally treated with acyclovir; Herpes-zoster traditionally treated with acyclovir;
however, may not be effective in pts treated long- however, may not be effective in pts treated long-
term with the oral form 2 term with the oral form 2 to resistance to resistance
Management
Management
! ! Moorthy Moorthy et al. Management of VZVR in AIDS. Br J et al. Management of VZVR in AIDS. Br J
Ophth Ophth, 1997. 20 pts (39 eyes); 11 pts using oral , 1997. 20 pts (39 eyes); 11 pts using oral
acyclovir at time of diagnosis acyclovir at time of diagnosis
! ! Retrospective chart review Retrospective chart review
! ! median median f/u f/u 6 months (1-26 months) 6 months (1-26 months)
! ! Objective: Investigate visual outcome Objective: Investigate visual outcome
! ! 2 week IV treatment 2 week IV treatment: :
! ! Acyclovir (10mg/kg Q8h) Acyclovir (10mg/kg Q8h)
! ! Ganciclovir Ganciclovir (5mg/kg Q12h x 2 weeks; then 5mg/kg/day) (5mg/kg Q12h x 2 weeks; then 5mg/kg/day)
! ! Foscarnet Foscarnet (180mg/kg/day in 2 or 3 divided doses) (180mg/kg/day in 2 or 3 divided doses)
! ! Ganciclovir Ganciclovir + + foscarnet foscarnet
Management
Management
! ! Results Results: :
! ! Rates of NLP Rates of NLP $ $: : acyclovir (9 of 10 eyes) & acyclovir (9 of 10 eyes) & foscarnet foscarnet (3 of (3 of
5 eyes) 5 eyes)
! ! V V
A A
> 20/200 > 20/200
! ! Rates of NLP Rates of NLP # #: : combination therapy (5 of 18 eyes) & combination therapy (5 of 18 eyes) &
ganciclovir ganciclovir (2 of 6 eyes) (2 of 6 eyes)
! ! V V
A A
> 20/200 > 20/200
! ! Combination therapy: 3 of 18 eyes Combination therapy: 3 of 18 eyes
! ! Ganciclovir Ganciclovir: 1 of 6 eyes : 1 of 6 eyes
! ! Conclusion: Treatment with IV combination therapy or Conclusion: Treatment with IV combination therapy or
ganciclovir ganciclovir associated with a better final associated with a better final v v
A A
VS acyclovir VS acyclovir
or or foscarnet foscarnet alone alone
Management
Management
! ! Ciulla Ciulla, et al. PORN: Successful treatment with , et al. PORN: Successful treatment with
combination antiviral therapy. combination antiviral therapy. Ophth Ophth Surgery & Surgery &
Lasers. 1998. Lasers. 1998. 6 pts with AIDS 6 pts with AIDS
! ! Retrospective chart review Retrospective chart review
! ! Median Median f/u f/u 29 weeks (27 -38 weeks) 29 weeks (27 -38 weeks)
! ! Objective: Assess 2-drug combination therapy Objective: Assess 2-drug combination therapy
! ! IV Treatment duration: median 29 weeks (27-38 weeks) IV Treatment duration: median 29 weeks (27-38 weeks)
! ! Ganciclovir Ganciclovir (5mg/kg Q12h) + acyclovir (500mg/m (5mg/kg Q12h) + acyclovir (500mg/m
2 2
Q8h) Q8h)
! ! Foscarnet Foscarnet (60mg/kg Q8-12h) + (60mg/kg Q8-12h) + ganciclovir ganciclovir
! ! Foscarnet Foscarnet + acyclovir + acyclovir
Management
Management
! ! Results Results: :
! ! All 6 pts had resolution of disease All 6 pts had resolution of disease
! ! 1 of 6 pts had recurrence 1 of 6 pts had recurrence
! ! At diagnosis 3 of 12 eyes without disease At diagnosis 3 of 12 eyes without disease " "
remained uninvolved remained uninvolved
! ! 10 of 12 eyes developed RD 10 of 12 eyes developed RD
! ! Conclusion: Prolonged combination therapy arrested Conclusion: Prolonged combination therapy arrested
progression of retinitis; maintained remission & prevented progression of retinitis; maintained remission & prevented
fellow eye involvement; does not prevent retinal fellow eye involvement; does not prevent retinal
detachment detachment
! ! Role of Role of ganciclovir ganciclovir intraocular implant & oral agents in intraocular implant & oral agents in
combination therapy is unclear combination therapy is unclear
Management
Management
! ! Intravitreal Intravitreal injection ( injection (ganciclovir ganciclovir & & foscarnet foscarnet); );
intravitreal intravitreal ganciclovir ganciclovir implant implant
! ! No protection for fellow eye No protection for fellow eye
Complications
Complications
! ! Retinal necrosis Retinal necrosis
! ! Retinal tears/holes Retinal tears/holes
! ! Rhegmatogenous Rhegmatogenous retinal detachment retinal detachment
Management
Management
! ! Prophylactic laser Prophylactic laser retinopexy retinopexy
! ! Engstrom Engstrom et al. 1994 et al. 1994
! ! 14 of 54 eyes: Laser 14 of 54 eyes: Laser
~ ~
1 week after diagnosis 1 week after diagnosis
! ! 93% developed a RD 93% developed a RD
! ! Median interval Median interval
~ ~
3 weeks 3 weeks
! ! significant difference: laser VS no laser: significant difference: laser VS no laser:
! ! Zone of involvement of RD Zone of involvement of RD
! ! Extent of RD Extent of RD
! ! Interval from diagnosis to RD Interval from diagnosis to RD
Management
Management
! ! Rhegmatogenous Rhegmatogenous retinal detachment retinal detachment
! ! Engstrom Engstrom et al. 1994 et al. 1994
! ! 43 of 65 eyes: Median interval 4 weeks 43 of 65 eyes: Median interval 4 weeks
! ! No relationship to extent of disease or disease activity No relationship to extent of disease or disease activity
! ! Vitrectomy/endolaser/silicone Vitrectomy/endolaser/silicone oil oil
! ! 16 of 43 eyes: Retinas successfully attached in all eyes 16 of 43 eyes: Retinas successfully attached in all eyes
! ! Re-detached in 4 eyes Re-detached in 4 eyes
! ! NLP in 56% (laser) VS 63% (no laser) NLP in 56% (laser) VS 63% (no laser)
Prognosis
Prognosis
! ! Visual prognosis is poor Visual prognosis is poor
! ! Macular involvement Macular involvement
! ! Ineffectiveness of antiviral agents Ineffectiveness of antiviral agents
! ! Recurrence Recurrence
! ! Engstrom Engstrom, et al. 1994 , et al. 1994
! ! At least 10 pts despite being on maintenance therapy At least 10 pts despite being on maintenance therapy
! ! Characterized by development of new disease foci Characterized by development of new disease foci
! ! In 6 pts associated with discontinuation/reduction in In 6 pts associated with discontinuation/reduction in
maintenance dose; median time to recurrence was maintenance dose; median time to recurrence was
2 weeks (1-6 weeks) 2 weeks (1-6 weeks)
! ! ~ 50% of individuals ~ 50% of individuals " " deceased 5 months after diagnosis deceased 5 months after diagnosis
Back To Our Patient
Back To Our Patient

! ! Patient admitted to medicine Patient admitted to medicine

! ! Infectious disease consulted Infectious disease consulted
! ! Received IV Received IV foscarnet foscarnet (40mg/kg Q12 x 14 days) (40mg/kg Q12 x 14 days)
! ! Progression of lesions Progression of lesions
! ! V V
A A
improved to 20/60 (+1.75) improved to 20/60 (+1.75)
! ! Discharged on oral acyclovir 800mg 5x day Discharged on oral acyclovir 800mg 5x day
Take Home Points
Take Home Points

! ! Progressive outer retinal necrosis is a rapidly Progressive outer retinal necrosis is a rapidly
progressive necrotizing retinitis occurring in progressive necrotizing retinitis occurring in
immunocompromised immunocompromised individuals, esp. AIDS individuals, esp. AIDS
pts pts
! ! Management is anecdotal: use of high-dose Management is anecdotal: use of high-dose
IV anti- IV anti-virals virals may be beneficial may be beneficial
! ! Poor visual prognosis Poor visual prognosis
References
References
! ! E-Medicine: Ocular manifestations of HIV E-Medicine: Ocular manifestations of HIV
! ! Forster et al. Rapidly PORN in AIDS. Am J Forster et al. Rapidly PORN in AIDS. Am J Ophth Ophth 110: 341. 1990 110: 341. 1990
! ! Moorthy Moorthy et al. Management of VZV retinitis in AIDS. Br J et al. Management of VZV retinitis in AIDS. Br J Ophth Ophth, 1997. , 1997.
! ! Walton et al. Walton et al. Fluorescein Fluorescein angiography in PORN. Retina 16: 1996 angiography in PORN. Retina 16: 1996
! ! Ciulla Ciulla, et al. The PORN: Successfully treatment with combination antiviral , et al. The PORN: Successfully treatment with combination antiviral
therapy. therapy. Ophth Ophth Surgery & Lasers. 1998 Surgery & Lasers. 1998
! ! BCSC. Retina & Vitreous. AAO. 2004-05 BCSC. Retina & Vitreous. AAO. 2004-05
! ! BCSC. BCSC. Uveitis Uveitis & Intraocular Inflammation. AAO. 2004-05 & Intraocular Inflammation. AAO. 2004-05
! ! Yanoff Yanoff. Ophthalmology, 2 . Ophthalmology, 2
nd nd
Ed. Ed. Mosby Mosby. 1121-22 . 1121-22
! ! Kanski Kanski. Clinical Ophthalmology, 5 . Clinical Ophthalmology, 5
th th
Ed. Butterworth Heinemann. 288-93. Ed. Butterworth Heinemann. 288-93.
2003 2003